PROJECT SUMMARY/ABSTRACT Temporomandibular disorders (TMDs) are a group of more than 30 human diseases, often characterized by joint degeneration with synovial inflammation, subchondral bone remodeling, cartilage degeneration, and pain. There is an urgent, unmet medical need to effectively manage and treat TMDs, preventing long-term pain and invasive procedures such as TMJ replacement. Our vision is to assemble a comprehensive and dynamic team of clinicians, research scientists, regulatory experts, and clinical trial specialists to advance basic and clinical research, research training, and evidence-based treatment for TMDs. Towards this end, we will develop a comprehensive and collaborative multi-institutional Center for TMD IMproving PAtient-Centered Translational Research (C-TMD IMPACT) that is driven by clinical needs, as defined by practicing clinicians. We will define C-TMD IMPACT’s future research priorities based on clinical relevance, scientific feasibility, patients’ needs, and likelihood of regulatory approval and commercialization. Ultimately, as part of the TMD IMPACT Collaborative, our collective expertise at C-TMD IMPACT will transform TMD management by identifying and validating therapeutic solutions via establishing well-defined procedures for successful experimental design, small and large animal models, in-depth translational assessment of research discoveries, product validation, manufacturing scale-up, regulatory approval, clinical testing, implementation, and training the future workforce for TMD studies. We propose the following Specific Aims: Specific Aim 1: Assemble a team of experts with integrated clinical, scientific/technical, and regulatory expertise to form C-TMD IMPACT. We will host one working retreat; one TMD-oriented research training and career development program; and bi-monthly teleconferences throughout the year to develop and refine the overall vision, roadmap, organizational structure, and operational procedures for C-TMD IMPACT. We will fully establish the necessary infrastructure to support TMD research, integrating existing resources for basic, translational, and clinical research as well as training the future workforce on our participating campuses. Specific Aim 2: Enable clinicians to define unmet clinical needs for managing and treating TMDs and engage with appropriate experts on product development and regulatory affairs to assess feasibility. According to these identified needs, we will develop the necessary technical approaches, protocols, and data management infrastructure. We will implement a multifaceted communications strategy to foster dialogue with the public, potential interdisciplinary research teams, and other members of the TMD IMPACT Collaborative.